This project explores the use of a novel biocompatible material (polyvinyl alcohol) for treatment of ischemic mitral regurgitation-a common valvular disorder which occurs following heart attacks. We plan on studying the properties of this biomaterial and its effect on the heart muscle and valvular function so that it can be used in the most effective way in patients with ischemic mitral regurgitation. Ischemic mitral regurgitation (MR) is a common complication of myocardial infarction that doubles late mortality. The fundamental mechanism underlying ischemic mitral regurgitation is distortion of the damaged heart wall, which pulls on the mitral valve leaflets and restricts their ability to close. We have shown that this process can be reversed by re-shaping the heart surgically with plication or with an external patch; these approaches, however, immobilize a large portion of the heart and require open-heart surgery. We propose to explore an innovative approach toward achieving this goal with the use of biomaterials that are specifically designed for injection into the myocardium with subsequent crosslinking once injected. This results in myocardial tissue bulking and repositioning of the infarcted myocardial wall with relief of LV distortion and deformation, thereby assuming a more normal shape that relieves the tension on the mitral leaflets. This approach also has the potential for minimally invasive implementation such as through percutaneous delivery. To achieve this synthesis of clinical problem and developmental techniques, this proposal will bring together expertise in several areas: quantitative analysis of the mitral valve in animal models by three-dimensional echocardiography, development of a biomaterial with physical and mechanical properties adapted to relieve ischemic distortion of the ventricle (Drs. Orhun Muratoglu and Gavin Brathwaite of Biomaterials Laboratory at MGH and Cambridge Polymer Group, Inc, Charlestown, MA), MRI diffusion imaging for assessment of changes in myocardial fiber architecture :(Dr. Van Wedeen) and cardiovascular physiology and surgery (Dr. Vlahakes). [unreadable] [unreadable] [unreadable]